Alpha-synuclein pathology driven impairment in adult neurogenesis was proposed as
a potential cause of, or at least contributor to, memory impairment observed in both
patients and animal models of Parkinson’s disease (PD) and Dementia with Lewy
Bodies (DLB). Mice overexpressing wild-type alpha-synuclein under the Thy-1 promoter
(Thy1-aSyn, line 61) uniquely replicate early cognitive deficits together with multiple
other characteristic motor and non-motor symptoms, alpha-synuclein pathology and
dopamine loss. Here we report overt intracellular accumulation of phosphorylated alphasynuclein
in the hippocampus of these transgenic mice. To test whether this alters adult
neurogenesis and total number of mature neurons, we employed immunohistochemistry
and an unbiased stereology approach to quantify the distinct neural progenitor cells and
neurons in the hippocampal granule cell layer and subgranular zone of 6 (prodromal
stage) and 16-month (dopamine loss) old Thy1-aSyn mice. Surprisingly, we observed
an increase in the number of early stage, i.e., Pax6 expressing, progenitors whereas the
numbers of late stage, i.e., Tbr2 expressing, progenitors and neurons were not altered.
Astroglia marker was increased in the hippocampus of transgenic mice, but this was
not specific to the regions where adult neurogenesis takes place, arguing against a
commitment of additional early stage progenitors to the astroglia lineage. Together, this
uncovers a novel aspect of alpha-synuclein pathology in adult neurogenesis. Studying
its mechanisms in Thy1-aSyn mice could lead to discovery of effective therapeutic
interventions for cognitive dysfunction in PD and DLB.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84510 |
| Date | 03 April 2023 |
| Creators | Bender, Hannah, Fietz, Simone A., Richter, Franziska, Stanojlovic, Milos |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2296-634X, 691560 |
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